Junctional Defect Research Articles

The junctional parenchymal defect: a sonographic variant of renal anatomy.

A triangular echogenic area in the upper pole renal parenchyma can be identified at times during routine sonography of the right kidney. Thirty such cases are presented. Occasionally similar echogenic defects in the parenchyma can be seen posteriorly in the lower pole and in the left kidney. These defects in the parenchyma result from normal extensions of the renal sinus of kidneys that have a distinct division of their upper and lower poles. This is due to partial fusion of two embryonic parenchymatous masses called renunculi. The defects in the parenchyma occur at the junction of the renunculi; hence we have termed them junctional parenchymal defects. In order to differentiate them from pathologic conditions, one must identify their characteristic location and demonstrate continuity with the renal sinus.

Correction of cell-cell communication defect by introduction of a protein kinase into mutant cells.

The cell-to-cell permeability of the junctions of various cultured mammalian cell types depends on the concentration of intracellular cyclic AMP [( cAMP]i). The permeability rises when the cells are supplied with exogenous cyclic AMP or when their cyclic AMP synthesis is stimulated with choleragen or hormones; it falls when [cAMP]i is lowered by application of serum or due to increase in cell density. The rise and fall in permeability take several hours to develop (the rise is protein synthesis-dependent) and they occur concurrently with the rise and fall in the number of intramembrane particles of the gap junctions, which probably embody the cell-to-cell channels. Is this permeability regulation mediated by phosphorylating protein kinase? In many eukaryotes, the cyclic AMP receptor is a protein kinase consisting of a pair of regulatory subunits and a pair of catalytic subunits. The latter dissociate from the holoenzyme as the cyclic AMP binds to the regulatory subunits and, in this dissociated form, catalyse the phosphorylation of the target. The regulatory subunit occurs in two isoenzyme forms, I and II. The catalytic subunit seems invariant; subunits from different isoenzymes can substitute for each other. We show here that a mutant cell lacking the isoenzyme I is deficient in permeable junctions, and that this junctional defect is corrected when the mutant is supplied with exogenous catalytic subunit.

Myasthenia gravis.

In myasthenia gravis, fatigability and persistent, often fatal weakness of voluntary muscles are attributable to dysfunction at the neuromuscular junction. The overall dysimmune state of the patient probably causes the junctional defect. Seventy percent of patients have thymic hyperplasia and 10%, thymoma. The atrophy of muscle fibers usually looks like denervation atrophy, and there are morphologic abnormalities of motor axon endings and the postsynaptic region of the muscle fiber. Electromyographic studies detect the neuromuscular junction defects: fatigue on repetitive stimulation and post-tetanic exhaustion. "Open-biopsy EMG" confirms that the commonly found electromyographic pattern comes from regions showing only denervation-like atrophy of muscle fibers. Other diagnostic tests include benefit from anticholinesterases and worsening by d-tubocurarine; the worsening of weakness by lactate infusion might serve as a diagnostic test. Treatment includes anticholinesterases, thymectomy, and the recently introduced long-term, high single dose, alternate-day prednisone program. Experienced 24-hour nursing surveillance is essential to treatment of the severely myasthenic patient.

Parallel correction of cancerous growth and of a genetic defect of cell-to-cell communication.

THREE strains of cells have recently been found which, unlike normal cells, do not make junctions of a kind that connects the cell interiors to each other1,2. These three strains are also cancerous1,2. We explore here whether the junctional defect is related to the cancerous state of these cells; we fuse cells of one of the strains with normal cells that make junctions and examine the junctional permeability and growth properties of the resulting hybrids. This approach is based on the findings of Harris and Klein and colleagues, and of Weiss, Todaro and Green, that tumorigenicity is markedly reduced3,4 and contact inhibition of growth resumed5 in hybrids between various kinds of cancer and normal cells. This also turned out to be the case with the present cell systems. The question is then, is the normalization of the growth properties associated with normalization of junctional connexion? The results show that both defects are corrected in the hybrids.